Disruption of intestinal barrier function associated with experimental colitis: possible role of mast cells.
The objective was to characterize changes in barrier and transport function in an experimental model of colitis, and to determine whether mast cells contribute to these changes. Colitis was induced in rats with intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNBS, 30 mg) in 50% ethanol. Controls received 0.9% saline or the ethanol vehicle alone. In vivo loop perfusion was used to assess colonic water flux (in microliter.cm-1.h-1) and lumen-to-blood 51Cr-labeled EDTA clearance (% administered dose) after TNBS. Myeloperoxidase (MPO) was used as an index of granulocyte influx. TNBS or its vehicle caused a marked decrease in water absorption and an increase in permeability at 4 h after administration compared with saline. Neither dexamethasone (anti-inflammatory control) nor doxantrazole (mast cell stabilizer) was able to attenuate these early changes likely caused by the vehicle. In contrast, at later times, TNBS (but not its vehicle) also increased 51Cr-EDTA permeability and decreased water absorption; both effects were significantly attenuated by dexamethasone or doxantrazole. These drugs also significantly reduced TNBS-induced MPO accumulation and release of rat mast cell protease II. We conclude that experimental colitis is associated with severe defects in intestinal transport and barrier functions and that mast cells may contribute to the pathogenesis of these changes.
Stein
J
J
Department of Medicine, University of California, School of Medicine, San Diego 92103, USA.
Ries
J
J
Barrett
K E
KE
D000818:Animals; D015415:Biomarkers; D001834:Body Water / Q000378:metabolism; D002860:Chromium Radioisotopes / Q000493:pharmacokinetics; D053818:Chymases; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000493:pharmacokinetics; D006098:Granulocytes / Q000502:physiology; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000032:analysis; D013892:Thioxanthenes / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid; D044004:Xanthones
D015415:Biomarkers; D002860:Chromium Radioisotopes; D013892:Thioxanthenes; D044004:Xanthones; D003907:Dexamethasone; D014302:Trinitrobenzenesulfonic Acid; D004492:Edetic Acid; D009195:Peroxidase; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; C010134:doxantrazole